Lin Lizhen, Ye Keng, Chen Fengbin, Xie Jingzhi, Chen Zhimin, Xu Yanfang
Department of Traditional Chinese Medicine, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
Blood Purification Research Center, Department of Nephrology, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
Front Genet. 2023 Apr 5;14:1119017. doi: 10.3389/fgene.2023.1119017. eCollection 2023.
Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a systemic autoimmune disease that may lead to end-stage renal disease. However, few specifific biomarkers are available for AAV-related renal injury. The aim of this study was to identify important biomarkers and explore new immune subtypes of AAV-related renal injury. In this study, messenger RNA expression profiles for antibody-associated vasculitis and AAV-associated kidney injury were downloaded from the Gene Expression Omnibus database. Weighted gene co-expression network analysis (WGCNA) was performed to identify the most relevant module genes to AAV. Key module genes from WGCNA were then intersected with AAV- and nephropathy-related genes from the Genecards database to identify key genes for AAV-associated kidney injury. Subsequently, the expression of key genes was validated in independent datasets and the correlation of genes with clinical traits of kidney injury was verified by the Nephroseq database. Finally, non-negative matrix factorization (NMF) clustering was performed to identify the immune subtypes associated with the key genes. Eight co-key genes (, , , , , , , and ) were identifified, and validated the expression levels independent datasets. Receiver operating characteristic curve analysis revealed that these eight genes have major diagnostic value as potential biomarkers of AAV-related renal injury. Through our comprehensive gene enrichment analyses, we found that they are associated with immune-related pathways. NMF clustering of key genes identified two and three immune-related molecular subtypes in the glomerular and tubular data, respectively. A correlation analysis with prognostic data from the Nephroseq database indicated that the expression of co-key genes was positively co-related with the glomerular filtration rate. Altogether, we identifified 8 valuable biomarkers that firmly correlate with the diagnosis and prognosis of AAV-related renal injury. These markers may help identify new immune subtypes for AAV-related renal injury.
抗中性粒细胞胞浆抗体(ANCA)相关性血管炎(AAV)是一种可能导致终末期肾病的系统性自身免疫性疾病。然而,针对AAV相关肾损伤的特异性生物标志物很少。本研究的目的是识别重要的生物标志物,并探索AAV相关肾损伤的新免疫亚型。在本研究中,从基因表达综合数据库下载了抗体相关性血管炎和AAV相关性肾损伤的信使RNA表达谱。进行加权基因共表达网络分析(WGCNA)以识别与AAV最相关的模块基因。然后将WGCNA中的关键模块基因与来自Genecards数据库的AAV和肾病相关基因进行交叉分析,以识别AAV相关肾损伤的关键基因。随后,在独立数据集中验证关键基因的表达,并通过Nephroseq数据库验证基因与肾损伤临床特征的相关性。最后,进行非负矩阵分解(NMF)聚类以识别与关键基因相关的免疫亚型。鉴定出8个共同关键基因(……此处原文8个基因未列出),并在独立数据集中验证了其表达水平。受试者工作特征曲线分析表明,这8个基因作为AAV相关肾损伤的潜在生物标志物具有重要诊断价值。通过我们全面的基因富集分析,我们发现它们与免疫相关途径有关。关键基因的NMF聚类在肾小球和肾小管数据中分别识别出两种和三种免疫相关分子亚型。与Nephroseq数据库的预后数据进行相关性分析表明,共同关键基因的表达与肾小球滤过率呈正相关。总之,我们鉴定出8个与AAV相关肾损伤的诊断和预后密切相关的有价值的生物标志物。这些标志物可能有助于识别AAV相关肾损伤的新免疫亚型。